Page 669 - Textbook of Pathology, 6th Edition

presence of antidiuretic hormone (ADH). Failure to achieve maintain constant plasma concentration and accurately timed 653
adequate urinary concentration can be due to either defects urine samples are collected. Inulin, a mixture of fructose
within the renal medulla (nephrogenic diabetes insipidus), or polymers, is considered the ideal substance for the clearance
due to the lack of ADH (central diabetes insipidus). test since it is filtered from the glomerulus and is excreted
Traditionally, urinary concentration is determined by unchanged in the urine.
specific gravity of the urine (normal range 1.003 to 1.030, ii) In creatinine clearance test, there is no need of intra-
average 1.018) which in cases of tubular disease remains venous infusion of creatinine since creatinine is normally
constant at approximately 1.010 regardless of changing levels released into plasma by muscle metabolism and a very small
of plasma hydration. However, determination of urinary fraction of this substance is secreted by the tubules. The
specific gravity provides only a rough estimate of osmolarity clearance of creatinine is determined by collecting urine over
of the urine. The tubular disease can be diagnosed in its early 24-hour period and a blood sample is withdrawn during the
stage by water deprivation (concentration) or water excess day. In spite of disadvantages like poor reproducibility and
(dilution) tests. secretion of creatinine by the tubules, the ‘endogenous’
i) In concentration test, an artificial fluid deprivation is creatinine clearance test is easy and routinely employed
induced in the patient for more than 20 hours. If the nephron method of estimating GFR.
is normal, water is selectively reabsorbed resulting in iii) In urea clearance test, the sensitivity is much less than
excretion of urine of high solute concentration (specific the creatinine or inulin clearance because plasma
gravity of 1.025 or more). However, if the tubular cells are concentration of urea is affected by a number of factors (e.g.
nonfunctional, the solute concentration of the urine will dietary protein, fluid intake, infection, trauma, surgery, and
remain constant regardless of stress of water deprivation. corticosteroids) and is partly reabsorbed by the tubules. Like
ii) In dilution test, an excess of fluid is given to the patient. in creatinine clearance, there is no need for intravenous
Normally, renal compensation should result in excretion of infusion of urea.
urine with high water content and lower solute concentration iv) Para-aminohippuric acid (PAH) clearance test is
(specific gravity of 1.003 or less). If the renal tubules are employed to measure renal blood flow (unlike the preceding
diseased, the concentration of solutes in the urine will remain tests which measure GFR). PAH when infused intravenously
constant irrespective of the excess water intake. is both filtered at the glomerulus as well as secreted by the CHAPTER 22
3. BLOOD CHEMISTRY. Impairment of renal function tubules and its clearance is measured by determining its
results in elevation of end-products of protein metabolism. concentration in arterial blood and urine. Normally, renal
This includes increased accumulation of certain substances blood flow is about 1200 ml per minute in an average adult.
in the blood, chiefly urea (normal range 20-40 mg/dl), blood
urea nitrogen (BUN) (normal range 10-20 mg/dl) and PATHOPHYSIOLOGY OF RENAL DISEASE:
creatinine (normal range 0.6-1.2 mg/dl). An increase of these RENAL FAILURE
end-products in the blood is called azotaemia. Traditionally, diseases of the kidneys are divided into 4 major
High levels of creatinine are associated with high levels groups according to the predominant involvement of
of β2-microglobulin in the serum as well as urine, a low- corresponding morphologic components:
molecular weight protein filtered excessively in the urine due 1. Glomerular diseases: These are most often immuno-
to glomerular disease or due to increased production by the logically-mediated and may be acute or chronic.
liver.
2. Tubular diseases: These are more likely to be caused by
4. RENAL CLEARANCE TESTS. A clearance test is toxic or infectious agents and are often acute. The Kidney and Lower Urinary Tract
employed to assess the rate of glomerular filtration and the 3. Interstitial diseases: These are likewise commonly due to
renal blood flow. The rate of this filtration can be measured toxic or infectious agents and quite often involve interstitium
by determining the excretion rate of a substance which is as well as tubules (tubulo-interstitial diseases).
filtered through the glomerulus but subsequently is neither 4. Vascular diseases: These include changes in the nephron
reabsorbed nor secreted by the tubules. The glomerular as a consequence of increased intra-glomerular pressure such
filtration rate (normal 120 ml/minute in an average adult) is as in hypertension or impaired blood flow.
usually equal to clearance of that substance and is calculated In addition, other diseases described in this chapter
from the following equation:
include: congenital anomalies, obstructive uropathy
UV (including urolithiasis) and tumours of the kidneys.
C = _______ where The major morphologic involvements of the kidneys in
P the initial stage is confined to one component (glomeruli,
C is the clearance of the substance in ml/ minute; tubules, interstitium or blood vessels), but eventually all
U is the concentration of the substance in the urine; components are affected leading to end-stage kidneys.
V is the volume of urine passed per minute; and Regardless of cause, renal disease usually results in the
P is the concentration of the substance in the plasma. evolution of one of the two major pathological syndromes:
The substances which are used for clearance tests include acute renal failure and chronic renal failure. The term ‘azotaemia’
inulin, mannitol, creatinine and urea. is used for biochemical abnormality characterised by
i) In inulin or mannitol clearance tests, an intravenous elevation of the blood urea nitrogen (BUN) and creatinine
infusion of the substance inulin or mannitol is given to levels, while ‘uraemia’ is defined as association of these